Hydroxychloroquine

Drug Levels and Effects:




Summary of Use during Lactation:


Early literature indicated some reluctance to allow breastfeeding during hydroxychloroquine use. Newer information indicates that infants exposed to hydroxychloroquine during breastfeeding receive only small amounts of the drug in breastmilk. In a small number of infants up to at least 1 year of age, careful follow-up found no adverse effects on growth, vision or hearing.[1][2]

A survey of US, Canadian, British and Mexican physician experts in the treatment of systemic lupus erythematosus completed prior to the publication of the above safety data indicated that 63% would allow breastfeeding in mothers who took an antimalarial during pregnancy and 53% would "often" or "always" advise a mother to breastfeed if the antimalarial were begun after delivery. Only 13% would have "never" advised breastfeeding in this circumstance.[3] Another review concluded that hydroxychloroquine could be used during lactation.[4]


Drug Levels:


Hydroxychloroquine is usually available as thesulfatesalt with hydroxychloroquine constituting about 75% of the labeled dose of hydroxychloroquinesulfate. It has a half-life of over a month. Some studies have not been clear about the salt form and dosage of the products being taken and others have sampled milk after only a few doses before steady state was reached. These flaws make interpretation of some of the data difficult.

Maternal Levels.

In a patient beginning therapy with 200 mg of hydroxychloroquine (salt unspecified) twice daily, the highest milk level detected was 10.6 mcg/L from 3 to 12 hours after the fourth dose. After the first 48 hours of treatment with a total dosage of 800 mg, a total of 3.2 mcg was excreted into her breastmilk. This amounted to 0.0003% of the mother's total dosage.[5] However, it is unlikely that steady state had been reached at this time.

A woman who had been breastfeeding for 9 months began taking hydroxychloroquinesulfate400 mg (equivalent to 310 mg hydroxychloroquine base) nightly. After 6 weeks of this regimen, steady-state milk levels were 1.46, 1.09, 1.09 and 0.85 mg/L at 2, 9.5, 14 after one dose and 17.7 hours after a dose on the next day. The authors estimated that the infant would receive 0.11 mg/kg daily or about 2% of the mother's weight-adjusted dosage.[6]

Two women who had taken hydroxychloroquine 200 mg (probablysulfateequivalent to 150 mg of base) once or twice daily (the report is unclear) before and during pregnancy had milk levels measured after delivery. Hydroxychloroquine levels in the two mothers were 344 and 1424 mcg/L at unspecified times after a dose. The authors estimated an infant intake of 0.06 and 0.2 mg/kg daily in the two infants.[7] These authors also reported two other women who had milk hydroxychloroquine levels of 1131 and 1392 mcg/L at unreported times after unspecified doses (presumably 200 to 400 mg daily). The authors estimated that these two infants would receive no more than 0.2 mg/kg daily via breastmilk.[8]

Numerous samples of milk were obtained from 6 women who were receiving 400 mg (n = 5) or 200 mg (n = 1) of hydroxychloroquine daily. The average milk level was of 376 mcg/L (range 20-1463 mcg/L) of hydroxychloroquine and of 36 mcg/L (range 11-111 mcg/L) of desethylchloroquine. The authors estimated that a fully breastfed infant would receive 1 mg of hydroxychloroquine and 0.066 mg of desethylchloroquine daily.[9]

Infant Levels.

Relevant published information was not found as of the revision date.


Effects in Breastfed Infants:


No adverse effects were reported in one 9-month-old breastfed infant whose mother was taking 310 mg hydroxychloroquine base daily for 6 weeks.[6]

Five mothers took hydroxychloroquine 200 mg daily during pregnancy and breastfeeding, one for 30 months. Flash electroretinograms performed on the infants were normal.[1][10]

Another group of investigators have reported numerous infants whose mother took hydroxychloroquine during pregnancy and were breastfed during maternal hydroxychloroquine use. An abstract reported 16 infants breastfed for 1 to 19 months and followed up at an average of 24 months (range 1 to 86 months) with no evidence of visual or hearing deficits.[11] In a letter they reported 8 breastfed infants followed up at 1, 6 and 12 months of age who had normal growth and development and who had thorough, normal eye examinations at 1 and 12 months of age.[12] In a case series, 13 mothers taking hydroxychloroquinesulfate200 mg daily breastfed their infants for an average of 2.8 months (range 1 to 6 months). None had evidence of retinal, motor or growth abnormalities during 12 months of follow-up. The authors conclude that the benefits of breastfeeding outweigh the risk of hydroxychloroquine.[2] It appears that the 8 infants reported in the letter were included among the 13 infants in the case series, but it is unclear whether the 16 infants reported in the abstract were part of the case series.


Possible Effects on Lactation:


Relevant published information was not found as of the revision date.


Alternate Drugs to Consider:


(Rheumatoid Arthritis) Auranofin,Etanercept,Gold Sodium Thiomalate,Infliximab,Methotrexate,Penicillamine,Sulfasalazine


References:


1. Cimaz R, Brucato A, Meregalli E et al. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Arthritis Rheum. 2004;50:3056-7. PMID:15457485
2. Motta M, Tincani A, Faden D et al. Follow-up of infants exposed to hydroxychloroquine given to mothers during pregnancy and lactation. J Perinatol. 2005;25:86-9. PMID:15496869
3. Al-Herz A, Schulzer M, Esdaile JM. Survey of antimalarial use in lupus pregnancy and lactation. J Rheumatol. 2002;29:700-6. PMID:11950010
4. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation. Arch Intern Med. 2000;160:610-9. PMID:10724046
5. Ostensen M, Brown ND, Chiang PK et al. Hydroxychloroquine in human breast milk. Eur J Clin Pharmacol. 1985; 28:357. PMID:4007043
6. Nation RL, Hackett LP, Dusci LJ et al. Excretion of hydroxychloroquine in human milk. Br J Clin Pharmacol. 1984;17:368-9. Letter.
7. Costedoat-Chalumeau N, Amoura Z, Aymard G et al. Evidence of transplacental passage of hydroxychloroquine in humans. Arthritis Rheum. 2002;46:1123-4. PMID:11953993
8. Costedoat-Chalumeau N, Amoura Z, Sebbough D et al. Electroretinograms of children born to mothers treated with hydroxychloroquine during pregnancy and breast-feeding: comment on the article by Costedoat-Chalumeau et al. Author reply. Arthritis Rheum. 2004;50:3057-8. PMID:15457485
9. Cissoko H, Rouger J, Zahr N, Darrouzain F, Jonville-Bera AP, Autret-Leca E. Breast milk concentrations of hydroxychloroquine. Fundam Clin Pharmacol. 2010;24 (Suppl. 1):420. Abstract.
10. Cimaz R, Brucato A, Meregalli E et al. Electroretinograms of children born from mothers treated with hydroxychloroquine (HCQ) during pregnancy and breast-feeding. Lupus 2004;13:755. Abstract.
11. Tincani A, Faden D, Lojacono A et al. Hydroxychloroquine in pregnant patients with rheumatic disease. Arthritis Rheum. 2001;44(9):S397. Abstract 2065.
12. Motta M, Tincani A, Faden D et al. Antimalarial agents in pregnancy. Lancet. 2002;359:524-5. PMID:11853823



Substance Identification:




Substance Name:

Hydroxychloroquine

CAS Registry Number:

118-42-3

Drug Class:


  • Antimalarials


  • Administrative Information:




    LactMed Record Number:


    290


    Last Revision Date:


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